RAB27A Increases Proliferation, Migration, Cell Invasion in Colorectal Cancer

RAB27A increases the proliferation, migration, and invasion of colon cancer cells after being suppressed by RAB27A knockdown, according to the results of a study published in Scientific Reports.

Investigators also found that RAB27A promotes ectopic expression.

The results show that RAB27A is of vital importance for colon cancer development and could be a prognostic indicator and potential therapeutic target for colorectal cancer, they said.

Colorectal cancer “arises when colonic epithelial cells acquire a series of genetic or epigenetic mutations that increase cell growth and survival,” according to investigators.

Identifying new genes associated with colorectal cancer development is essential for early diagnosis and treatment, investigators said.

Rab proteins have been found to function as onco-proteins in cancer development, with the knockdown of RAB10 stopping the growth cycle and colony formation and promoting cell apoptosis in hepatocellular carcinoma cells. Rab27 is a sub-group in the Rab protein family, containing RAB27A. They have also been known to be involved in regulating cancer development.

RAB27A has been reported to facilitate breast cancer progression by promoting cell invasion and metastasis. It has also been linked to gliomas and melanoma, acting as an onco-protein in promoting human cancer development.

Investigators reported that previous findings have shown mixed results in the role of the protein in mediating colorectal cancer progression.

In a previous study by the same investigators, they established that RAB27A showed relatively high expression levels of SW480 and low expression levels in RKO. It was also indicated that the invasion ability, migration, and proliferation rate, were higher in SW480 cells than in RKO cells, which investigators thought pointed to RAB27A being positively correlated.

Investigators selected SW480 and RKO as cell models for RAB27A knockdown and overexpression, respectively.

The SW480 cells were transfected with RAB27A shRNA plasmid, while the RKO cells were transfected with Flag-tag RAB27A plasmid. Investigators used geneticin to select cell clones that stabilized neo gene.

They found that the expression levels of RAB274 mRNA and protein were significantly lower in RAB27A knockdown SW480 cells than in the control cells. Additionally, the levels increased in RKO cells stably transfected compared with the control cells.

In this study, the optical density value was significantly lower in RAB27A knockdown SW480 cells compared with the negative control cells, which showed that the knockdown inhibits cell growth. Further, the optical density value in RKO cells was significantly higher than the negative control cells, which indicated that the RAB27A ectopic expression promotes RKO cell growth.

Additionally, investigators used the stable cell lines of knockdown and ectopic expression to see the effect of RAB27A on cell migration and invasion.

They found that RAB27A knockdown cells were significantly lower than in the negative control group, which shows RAB27A is essential in mediating the migration of colorectal cancer cells. In RKO cells, it was confirmed that RAB27A contributes to cell migration.

Furthermore, investigators found that in SW480 cell invasion and RKO cell invasion, RAB27A inhibited and facilitated overexpression in the cells, respectively.

Reference

Li Q, Zhao H, Dong W, Guan N, et al. RAB27A promotes the proliferation and invasion of colorectal cancer cells. Sci Rep. 2022;12(1):19359. doi: 10.1038/s41598-022-23696-7